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The Effect of Alterations of Schizophrenia-Associated Genes on Gamma Band Oscillations

View ORCID ProfileChristoph Metzner, Tuomo Mäki-Marttunen, Gili Karni, Hana McMahon-Cole, Volker Steuber
doi: https://doi.org/10.1101/2020.09.28.316737
Christoph Metzner
1Neural Information Processing Group, Institute of Software Engineering and Theoretical Computer Science, Technische Universität Berlin, Berlin, Germany
2Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield, United Kingdom
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  • ORCID record for Christoph Metzner
  • For correspondence: christoph.metzner@gmail.com
Tuomo Mäki-Marttunen
3Department of Computational Physiology, Simula Research Laboratory, Oslo, Norway
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Gili Karni
1Neural Information Processing Group, Institute of Software Engineering and Theoretical Computer Science, Technische Universität Berlin, Berlin, Germany
4Minerva Schools at KGI, San Francisco, USA
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Hana McMahon-Cole
1Neural Information Processing Group, Institute of Software Engineering and Theoretical Computer Science, Technische Universität Berlin, Berlin, Germany
4Minerva Schools at KGI, San Francisco, USA
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Volker Steuber
2Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield, United Kingdom
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Abstract

Abnormalities in the synchronized oscillatory activity of neurons in general and, specifically in the gamma band, might play a crucial role in the pathophysiology of schizophrenia. While these changes in oscillatory activity have traditionally been linked to alterations at the synaptic level, we demonstrate here, using computational modeling, that common genetic variants of ion channels can contribute strongly to this effect. Our model of primary auditory cortex highlights multiple schizophrenia-associated genetic variants that reduce gamma power in an auditory steady-state response task. Furthermore, we show that combinations of several of these schizophrenia-associated variants can produce similar effects as the more traditionally considered synaptic changes. Overall, our study provides a mechanistic link between schizophrenia-associated common genetic variants, as identified by genome-wide association studies, and one of the most robust neurophysiological endophenotypes of schizophrenia.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted October 05, 2020.
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The Effect of Alterations of Schizophrenia-Associated Genes on Gamma Band Oscillations
Christoph Metzner, Tuomo Mäki-Marttunen, Gili Karni, Hana McMahon-Cole, Volker Steuber
bioRxiv 2020.09.28.316737; doi: https://doi.org/10.1101/2020.09.28.316737
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The Effect of Alterations of Schizophrenia-Associated Genes on Gamma Band Oscillations
Christoph Metzner, Tuomo Mäki-Marttunen, Gili Karni, Hana McMahon-Cole, Volker Steuber
bioRxiv 2020.09.28.316737; doi: https://doi.org/10.1101/2020.09.28.316737

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